ArticleNature ecology & evolution2018
Multinucleotide mutations cause false inferences of lineage-specific positive selection.
Article in Nature ecology & evolution, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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76 citing papers in PubMed.
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- Epistasis among clustered lineage-specific amino acid substitutions in the Drosophila Trio protein.PLoS genetics · 2026Article
- Concatenation, Conflict, and Complexity: Genealogical Heterogeneity Mimics Substitutional Heterogeneity for Nucleotide Model Selection.Journal of molecular evolution · 2026Article
- Calibrating and documenting host-switching and evolution of incompatibility loci for two closely relatedbioRxiv : the preprint server for biology · 2026Article
- The performance of genetic-constraint metrics varies significantly across the human noncoding genome.bioRxiv : the preprint server for biology · 2026Article
- Molecular Mechanisms of Venom Diversity.Toxins · 2025Review
- Highly Recurrent Multinucleotide Mutations in SARS-CoV-2.Molecular biology and evolution · 2025Article
- Detecting Interspecific Positive Selection Using Convolutional Neural Networks.Molecular biology and evolution · 2025Article
- Comparative Phylogenetics Reveal Clade-specific Drivers of Recombination Rate Evolution Across Vertebrates.Molecular biology and evolution · 2025Article
- Positive Selection on Mammalian Immune Genes-Effects of Gene Function and Selective Constraint.Molecular biology and evolution · 2025Article
- Dinucleotide codon substitutions as a signature of diversifying selection inFrontiers in molecular biosciences · 2025Article
- Gene loss and relaxed selection ofProceedings. Biological sciences · 2024Article
- Rapid evolution of genes with anti-cancer functions during the origins of large bodies and cancer resistance in elephants.bioRxiv : the preprint server for biology · 2024Article
- The Mutational Road not Taken: Using Ancestral Sequence Resurrection to Evaluate the Evolution of Plant Enzyme Substrate Preferences.Genome biology and evolution · 2024Article
- Signatures of Extreme Longevity: A Perspective from Bivalve Molecular Evolution.Genome biology and evolution · 2023Article
- Chromosome-level Asian elephant genome assembly and comparative genomics of long-lived mammals reveal the common substitutions for cancer resistance.Aging cell · 2023Article
- PhyloAcc-GT: A Bayesian Method for Inferring Patterns of Substitution Rate Shifts on Targeted Lineages Accounting for Gene Tree Discordance.Molecular biology and evolution · 2023Article
- Evolutionary Shortcuts via Multinucleotide Substitutions and Their Impact on Natural Selection Analyses.Molecular biology and evolution · 2023Article
16 more citing papers are in PubMed but not listed here.
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3 authors.
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Abstract
Phylogenetic tests of adaptive evolution, such as the widely used branch-site test (BST), assume that nucleotide substitutions occur singly and independently. Recent research has shown that errors at adjacent sites often occur during DNA replication, and the resulting multinucleotide mutations (MNMs) are overwhelmingly likely to be non-synonymous. To evaluate whether the BST misinterprets sequence patterns produced by MNMs as false support for positive selection, we analysed two genome-scale datasets-one from mammals and one from flies. We found that codons with multiple differences account for virtually all the support for lineage-specific positive selection in the BST. Simulations under conditions derived from these alignments but without positive selection show that realistic rates of MNMs cause a strong and systematic bias towards false inferences of selection. This bias is sufficient under empirically derived conditions to produce false positive inferences as often as the BST infers positive selection from the empirical data. Although some genes with BST-positive results may have evolved adaptively, the test cannot distinguish sequence patterns produced by authentic positive selection from those caused by neutral fixation of MNMs. Many published inferences of adaptive evolution using this technique may therefore be artefacts of model violation caused by unincorporated neutral mutational processes. We introduce a model that incorporates MNMs and may help to ameliorate this bias.
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